The present application represents a resubmission (01A1) of a COBRE application wherein we have addressed all concerns noted by reviewers (see Introduction). Revised individual project proposals are each preceded by an Introduction in which COBRE Investigators respond to Project Critiques provided by reviewers. The primary purpose of this renewal application continues to be fostering of health-related research and mentoring-enhanced competitiveness of junior, unfunded investigators. In this renewal application we have included proposals from: 2 junior investigators who have not previously been a PI on a funded research project grant or program project grant; 2 early career investigators who were COBRE supported during our initial funding period, and who were successful in obtaining independent funding from the NIH (R01 and K02); a senior investigator whose proposal will facilitate a mid-career research transition; and a pilot project from a clinical junior investigator seeking to redefine his academic career as a clinical research scientist. Two (2) new faculty lines, representing sustained commitment from the university, have been pledged as part of this competitive renewal application. Two junior faculty who complement the thematic scope of our COBRE will thus be recruited and will be COBRE-supported. Each of these investigators will be mentored by an established, well-funded senior biomedical research scientist recognized for his/her scientific expertise in the area of the COBRE investigator's research proposal. The program continues to be led by Robert M. Greene, Ph.D., an established biomedical research scientist, well recognized for his extensive expertise central to the research theme of the proposalmolecular mechanisms underlying developmental defects. This renewal application, if funded, will 1) substantially enhance the research career development and research competitiveness of no less than five (5) junior investigators, two early career investigators, and one senior investigator, and 2) promote the development and enhance the evolution of our Center such that it will be able to successfully compete for independent Center and/or program project funding. A detailed plan for each COBRE investigator's research career development has been formulated; expectations and objectives for achieving independent funding are clearly articulated; clear and tangible evidence of continuing and expanded institutional commitment is documented; excellent research resources and a supportive intellectual environment exists.